HIV (Human Immunodeficiency Virus (type 1)) belonging to retrovirus is a causative virus of AIDS (Acquired Immunodeficiency Syndrome).
HIV targets CD4 positive cell groups such as helper T cell, macrophage and dendritic cell, and destroys these immunocompetent cells to cause immunodeficiency.
Accordingly, a pharmaceutical agent that eradicates HIV in the body or suppresses its growth is effective for the treatment or prophylaxis of AIDS.
HIV possesses a bimolecular RNA gene in a shell, and which is covered with an envelope protein. The RNA codes for several enzymes (protease, reverse transcriptase, integrase) characteristic of the virus, and the like. Translated reverse transcriptase and integrase are present in the shell, and protease is present inside and outside the shell.
HIV attaches to and invades a host cell, causes uncoating, and releases a complex of RNA and integrase and the like into the cytoplasm. From the RNA, DNA is transcribed by reverse transcriptase, and a full length double stranded DNA is produced. The DNA is imported into the nucleus of the host cell and integrated by integrase into the DNA of the host cell. The integrated DNA is converted to an mRNA by polymerase of the host cell, from which mRNA various proteins necessary for forming a virus are synthesized by HIV protease and the like, and a virus particle is finally formed, which then undergoes budding and its release.
These virus specific enzymes are considered to be essential for the growth of HIV. These enzymes are drawing attention as the target of the development of antiviral agents, and several anti-HIV agents have been already developed.
For example, zidovudine, didanosine, lamivudine and the like have been already on the market as reverse transcriptase inhibitors, and indinavir, nelfinavir and the like as protease inhibitors.
In addition, a multiple drug combination therapy concurrently using these pharmaceutical agents has been employed. For example, a combined use of two reverse transcriptase inhibitors (zidovudine and didanosine), and a combined use of three agents of reverse transcriptase inhibitors (zidovudine and lamivudine) and a protease inhibitor (nelfinavir) and the like have been clinically applied. Such multiple drug combination therapy is becoming a mainstream of AIDS therapy (see e.g., Guidelines for the Use of Antiretroviral Agents in HIV-Infected Adults and Adlescent. Aug. 13, 2001).
However, some of these pharmaceutical agents are known to cause side effects such as liver function failure, central nervous disorders (e.g., vertigo), and the like. In addition, acquisition of resistance to a pharmaceutical agent causes a problem. Even worse, emergence of an HIV that shows multiple drug resistance in a multiple drug combination therapy has been known.
Under the circumstances, a further development of a novel pharmaceutical agent, particularly a development of an anti-HIV agent based on a new mechanism, has been desired, wherein a development of an anti-HIV agent having an integrase inhibitory activity is expected, because an integrase characteristic of retrovirus is an essential enzyme for the growth of HIV.
Nevertheless, an effective integrase inhibitor has not been found as yet.
Known antiviral agents comparatively similar to the anti-HIV agent of the present invention are described in the following.
WO2004/046115 describes compound A below and the like as anti-HIV agents having an integrase inhibitory activity (see WO2004/046115 (page 134, Example 1-99)).

However, this publication does not include the quinolizinone compound disclosed in the present specification, or any description suggestive thereof.
In addition, JP-A-2004-502771 (patent family: WO2002/004445) describes compound B below and the like as antiviral agents, particularly as agents against herpes viruses, and compound C below as intermediates thereof (see JP-A-2004-502771 (page 85, Example 7)).

Moreover, JP-A-2004-502770 (patent family: WO2002/004444) describes compound D below and the like as antiviral agents, particularly as agents against herpes viruses (see JP-A-2004-502770 (page 57, formula AI.8)). In addition, WO2004/019933 describes compound D below and the like as therapeutic agents for atherosclerosis and restenosis (see WO2004/019933 (page 64, compound (52))).

However, these publications do not include the quinolizinone compound disclosed in the present specification, or any description suggestive thereof.
Now, known compounds comparatively similar to the compound of the present invention are described in the following.
WO2003/029253 (patent family: EP1437354) describes compound E below and the like as compounds having an antibacterial activity (see WO2003/029253 (page 54, Example 119)).

However, this publication does not describe the quinolizinone compound disclosed in the present specification, nor the antiviral activity of the quinolizinone compound, or anything suggestive thereof.
Besides these, there are many antibacterial agents having a cyclic substituent (e.g., pyrrolidin-1-yl group) at the 8-position of quinolizinone skeleton. However, those antibacterial agents are different from the quinolizinone compound disclosed in the present specification in both the chemical structure and use thereof.
In addition, JP-B-6-49701 (patent family: EP157346) describes the following compound F, compound G and the like as compounds having an inhibitory activity against allergies and ulcers (see JP-B-6-49701 (pages 15-16, Example 3, (1) and (4))).

Moreover, WO2000/17197 describes the following compound H, compound i and the like as anticancer agents having an integrin inhibitory action, or vascular vessel regeneration inhibitors having an integrin inhibitory action (see WO2000/17197 (compound XIII at pages 71-74 and compound XLI at page 102)).

However, these publications do not describe the quinolizinone compound disclosed in the present specification, nor the antiviral activity of the quinolizinone compound, nor anything suggestive thereof.